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Autonomic Dysfunction in Hypersomnia

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Abstract

Purpose of Review

This article provides a comprehensive overview of the literature on autonomic dysfunctions in central disorders of hypersomnolence: narcolepsy type 1 and type 2, idiopathic hypersomnia, and the Kleine-Levin syndrome. Clinical implications are discussed.

Recent Findings

The interactions between the autonomic nervous system and central disorders of hypersomnolence are complex. Patients affected with these rare sleep diseases often report autonomic symptoms. Recent studies systematically assessed these symptoms in large cohorts of well-characterized patients, and some studies objectified autonomic disturbances during wakefulness and sleep, mostly with indirect measures.

Summary

Autonomic impairment is frequent in central disorders of hypersomnolence, and the pathophysiological mechanisms underlying this dysfunction are not yet fully elucidated. In narcolepsy type 1, the deficiency in orexin/hypocretin neurons could play a role, and that has been confirmed in animal models of the disease. Management of central disorders of hypersomnolence is nowadays only symptomatic, with wake-promoting agents, often psychostimulants. Further research is needed to understand the consequences of these medications on the autonomic nervous system and their possible relation to long-term cardiovascular risk.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Calandra-Buonaura G, Provini F, Guaraldi P, Plazzi G, Cortelli P. Cardiovascular autonomic dysfunctions and sleep disorders. Sleep Med Rev. 2016;26:43–56.

    Article  PubMed  Google Scholar 

  2. AASM: American Academy of Sleep Medicine. ICSD-3: International Classification of Sleep Disorders, 3rd ed. American Academy of Sleep Medicine; 2014.

  3. Dauvilliers Y, Barateau L. Narcolepsy and other central hypersomnias. Continuum (Minneap Minn). 2017;23:989–1004.

  4. Lammers GJ, Bassetti CLA, Dolenc-Groselj L, et al. Diagnosis of central disorders of hypersomnolence: a reappraisal by European experts. Sleep Med Rev. 2020;52:101306.

    Article  PubMed  Google Scholar 

  5. Dauvilliers Y, Barateau L, Lopez R, Rassu AL, Chenini S, Beziat S, Jaussent I. Narcolepsy severity scale: a reliable tool assessing symptom severity and consequences. Sleep. 2020;43:zsaa009. https://doi.org/10.1093/sleep/zsaa009

  6. Barateau L, Lopez R, Chenini S, Rassu AL, Mouhli L, Dhalluin C, Jaussent I, Dauvilliers Y. Linking clinical complaints and objective measures of disrupted nighttime sleep in narcolepsy type 1. Sleep. 2022;45:zsac054.

  7. Bassetti CLA, Adamantidis A, Burdakov D, et al. Narcolepsy - clinical spectrum, aetiopathophysiology, diagnosis and treatment. Nat Rev Neurol. 2019;15:519–39.

    Article  PubMed  Google Scholar 

  8. Barateau L, Pizza F, Plazzi G, Dauvilliers Y. Narcolepsy. J Sleep Res. 2022;15(9):519.

    Google Scholar 

  9. Peyron C, Tighe DK, van den Pol AN, de Lecea L, Heller HC, Sutcliffe JG, Kilduff TS. Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci. 1998;18:9996–10015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Pizza F, Barateau L, Dauvilliers Y, Plazzi G. The orexin story, sleep and sleep disturbances. J Sleep Res. 2022;31:e13665.

    Article  PubMed  Google Scholar 

  11. • Bastianini S, Silvani A, Berteotti C, Elghozi J-L, Franzini C, Lenzi P, Lo Martire V, Zoccoli G. Sleep related changes in blood pressure in hypocretin-deficient narcoleptic mice. Sleep. 2011;34:213–8.

  12. Alvente S, Berteotti C, Bastianini S, Lo Martire V, Matteoli G, Silvani A, Zoccoli G. Autonomic mechanisms of blood pressure Alterations during sleep in orexin/hypocretin-deficient narcoleptic mice. Sleep. 2021;44:zsab022. https://doi.org/10.1093/sleep/zsab022

  13. Barateau L, Lopez R, Dauvilliers Y. Treatment options for narcolepsy. CNS Drugs. 2016;30:369–79.

    Article  CAS  PubMed  Google Scholar 

  14. Plazzi G, Moghadam KK, Maggi LS, et al. Autonomic disturbances in narcolepsy. Sleep Med Rev. 2011;15:187–96.

    Article  PubMed  Google Scholar 

  15. •Barateau L, Chenini S, Evangelista E, Jaussent I, Lopez R, Dauvilliers Y. Clinical autonomic dysfunction in narcolepsy type 1. Sleep. 2019;42:zsz187. https://doi.org/10.1093/sleep/zsz187

  16. Miglis MG. Autonomic dysfunction in primary sleep disorders. Sleep Med. 2016;19:40–9.

    Article  PubMed  Google Scholar 

  17. Rocchi C, Placidi F, Del Bianco C, Liguori C, Pisani A, Mercuri NB, Izzi F. Autonomic symptoms, cardiovascular and sudomotor evaluation in de novo type 1 narcolepsy. Clin Auton Res. 30:557–62. https://doi.org/10.1007/s10286-020-00718-w

  18. Berteotti C, Silvani A. The link between narcolepsy and autonomic cardiovascular dysfunction: a translational perspective. Clin Auton Res. 2018;30:557–562. https://doi.org/10.1007/s10286-017-0473-z

  19. • Dauvilliers Y, Jaussent I, Krams B, Scholz S, Lado S, Levy P, Pepin JL. Non-dipping blood pressure profile in narcolepsy with cataplexy. PLoS ONE. 2012;7:e38977. (This study, together with ref. 20 below, was the first to translate to adult patients with NT1, the sleep-related cardiovascular alteration previously obtained in animal models of orexin deficiency (cf. ref. 11).)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. • Grimaldi D, Calandra-Buonaura G, Provini F, Agati P, Pierangeli G, Franceschini C, Barletta G, Plazzi G, Montagna P, Cortelli P. Abnormal sleep-cardiovascular system interaction in narcolepsy with cataplexy: effects of hypocretin deficiency in humans. Sleep. 2012;35:519–28. (This study, together with ref. 19 above, was the first to translate to adult patients with NT1, the sleep-related cardiovascular alteration previously discovered in animal models of orexin deficiency (cf. ref. 11).)

    Article  PubMed  PubMed Central  Google Scholar 

  21. Sieminski M, Partinen M. “Non-dipping” is equally frequent in narcoleptic patients and in patients with insomnia. Sleep Biol Rhythms. 2016;14:31–6.

    Article  PubMed  Google Scholar 

  22. Ohayon MM. Narcolepsy is complicated by high medical and psychiatric comorbidities: a comparison with the general population. Sleep Med. 2013;14:488–92.

    Article  PubMed  Google Scholar 

  23. Jennum PJ, Plazzi G, Silvani A, Surkin LA, Dauvilliers Y. Cardiovascular disorders in narcolepsy: review of associations and determinants. Sleep Med Rev. 2021;58:101440.

    Article  PubMed  Google Scholar 

  24. •Vandi S, Rodolfi S, Pizza F, Moresco M, Antelmi E, Ferri R, Mignot E, Plazzi G, Silvani A. Cardiovascular autonomic dysfunction, altered sleep architecture, and muscle overactivity during nocturnal sleep in pediatric patients with narcolepsy type 1. Sleep. 2019;42:zsz169. https://doi.org/10.1093/sleep/zsz169

  25. • Donadio V, Liguori R, Vandi S, Giannoccaro MP, Pizza F, Leta V, Plazzi G. Sympathetic and cardiovascular changes during sleep in narcolepsy with cataplexy patients. Sleep Med. 2014;15:315–21. (This study measured muscle sympathetic nerve activity together with blood pressure and heart rate during sleep in adult patients with NT1.)

    Article  PubMed  Google Scholar 

  26. Sieminski M, Chwojnicki K, Sarkanen T, Partinen M. The relationship between orexin levels and blood pressure changes in patients with narcolepsy. PLoS ONE. 2017;12:e0185975.

    Article  PubMed  PubMed Central  Google Scholar 

  27. • Bosco A, Lopez R, Barateau L, Chenini S, Pesenti C, Pépin J-L, Jaussent I, Dauvilliers Y. Effect of psychostimulants on blood pressure profile and endothelial function in narcolepsy. Neurology. 2018;90:e479–e491. (This study revealed that pharmacological therapy may adversely impact blood pressure control in adult patients with NT1.)

  28. Silvani A, Bastianini S, Berteotti C, Lo Martire V, Zoccoli G. Control of cardiovascular variability during undisturbed wake-sleep behavior in hypocretin-deficient mice. Am J Physiol Regul Integr Comp Physiol. 2012;302:R958-964.

    Article  CAS  PubMed  Google Scholar 

  29. Ferini-Strambi L, Spera A, Oldani A, Zucconi M, Bianchi A, Cerutti S, Smirne S. Autonomic function in narcolepsy: power spectrum analysis of heart rate variability. J Neurol. 1997;244:252–5.

    Article  CAS  PubMed  Google Scholar 

  30. Fronczek R, Overeem S, Reijntjes R, Lammers GJ, van Dijk JG, Pijl H. Increased heart rate variability but normal resting metabolic rate in hypocretin/orexin-deficient human narcolepsy. J Clin Sleep Med. 2008;4:248–54.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Silvani A, Grimaldi D, Barletta G, Bastianini S, Vandi S, Pierangeli G, Plazzi G, Cortelli P. Cardiovascular variability as a function of sleep-wake behaviour in narcolepsy with cataplexy. J Sleep Res. 2013;22:178–84.

    Article  PubMed  Google Scholar 

  32. Antelmi E, Plazzi G, Pizza F, Vandi S, Aricò D, Ferri R. Impact of acute administration of sodium oxybate on heart rate variability in children with type 1 narcolepsy. Sleep Med. 2018;47:1–6.

    Article  PubMed  Google Scholar 

  33. Donadio V, Liguori R, Vandi S, Pizza F, Dauvilliers Y, Leta V, Giannoccaro MP, Baruzzi A, Plazzi G. Lower wake resting sympathetic and cardiovascular activities in narcolepsy with cataplexy. Neurology. 2014;83:1080–6.

  34. • Sorensen GL, Knudsen S, Petersen ER, Kempfner J, Gammeltoft S, Sorensen HBD, Jennum P. Attenuated heart rate response is associated with hypocretin deficiency in patients with narcolepsy. Sleep. 2013;36:91–8. (This study found evidence of blunted changes in heart rate associated with sleep microstructural events in adult patients with NT1, in line with results from Ref. 36.)

  35. van der Meijden WP, Fronczek R, Reijntjes RHAM, Corssmit EPM, Biermasz NR, Lammers GJ, van Dijk JG, Thijs RD. Time- and state-dependent analysis of autonomic control in narcolepsy: higher heart rate with normal heart rate variability independent of sleep fragmentation. J Sleep Res. 2015;24:206–14.

    Article  PubMed  Google Scholar 

  36. • Dauvilliers Y, Pennestri M-H, Whittom S, Lanfranchi PA, Montplaisir JY. Autonomic response to periodic leg movements during sleep in narcolepsy-cataplexy. Sleep. 2011;34:219–23. (This study found evidence of blunted changes in heart rate associated with periodic leg movements during sleep in adult patients with NT1, in line with results from Ref. 34.)

  37. de Zambotti M, Pizza F, Covassin N, Vandi S, Cellini N, Stegagno L, Plazzi G. Facing emotions in narcolepsy with cataplexy: haemodynamic and behavioural responses during emotional stimulation. J Sleep Res. 2014;23:432–40.

    Article  PubMed  Google Scholar 

  38. Grimaldi D, Pierangeli G, Barletta G, Terlizzi R, Plazzi G, Cevoli S, Franceschini C, Montagna P, Cortelli P. Spectral analysis of heart rate variability reveals an enhanced sympathetic activity in narcolepsy with cataplexy. Clin Neurophysiol. 2010;121:1142–7.

    Article  CAS  PubMed  Google Scholar 

  39. Martelli D, Silvani A, McAllen RM, May CN, Ramchandra R. The low frequency power of heart rate variability is neither a measure of cardiac sympathetic tone nor of baroreflex sensitivity. Am J Physiol Heart Circ Physiol. 2014;307:H1005-1012.

    Article  CAS  PubMed  Google Scholar 

  40. Grassi G, Seravalle G, Cattaneo BM, Bolla GB, Lanfranchi A, Colombo M, Giannattasio C, Brunani A, Cavagnini F, Mancia G. Sympathetic activation in obese normotensive subjects. Hypertens. 1995;25:560–3.

    Article  CAS  Google Scholar 

  41. Kok SW, Overeem S, Visscher TLS, Lammers GJ, Seidell JC, Pijl H, Meinders AE. Hypocretin deficiency in narcoleptic humans is associated with abdominal obesity. Obes Res. 2003;11:1147–54.

    Article  CAS  PubMed  Google Scholar 

  42. Kotagal S, Krahn LE, Slocumb N. A putative link between childhood narcolepsy and obesity. Sleep Med. 2004;5:147–50.

    Article  PubMed  Google Scholar 

  43. • Schuld A, Hebebrand J, Geller F, Pollmächer T. Increased body-mass index in patients with narcolepsy. Lancet. 2000;355:1274–5. (This study provided one of the first demonstrations of metabolic alterations associated with NT1.)

    Article  CAS  PubMed  Google Scholar 

  44. • Dauvilliers Y, Barateau L, Middleton B, van der Veen DR, Skene DJ. Metabolomics signature of patients with narcolepsy. Neurol. 2022;98:e493–505. (This study provided an in-depth view of the metabolic changes associated with NT1 taking advantage of cutting-edge metabolomics.)

    Article  CAS  Google Scholar 

  45. Chabas D, Foulon C, Gonzalez J, Nasr M, Lyon-Caen O, Willer J-C, Derenne J-P, Arnulf I. Eating disorder and metabolism in narcoleptic patients. Sleep. 2007;30:1267–73.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Dahmen N, Tonn P, Messroghli L, Ghezel-Ahmadi D, Engel A. Basal metabolic rate in narcoleptic patients. Sleep. 2009;32:962–4.

    PubMed  PubMed Central  Google Scholar 

  47. Kreier F, Fliers E, Voshol PJ, et al. Selective parasympathetic innervation of subcutaneous and intra-abdominal fat–functional implications. J Clin Invest. 2002;110:1243–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Enevoldsen LH, Tindborg M, Hovmand NL, Christoffersen C, Ellingsgaard H, Suetta C, Stallknecht BM, Jennum PJ, Kjær A, Gammeltoft S. Functional brown adipose tissue and sympathetic activity after cold exposure in humans with type 1 narcolepsy. Sleep. 2018;41:zsy092.

    Article  Google Scholar 

  49. Sansa G, Iranzo A, Santamaria J. Obstructive sleep apnea in narcolepsy. Sleep Med. 2010;11:93–5.

    Article  PubMed  Google Scholar 

  50. Maski K, Mignot E, Plazzi G, Dauvilliers Y. Disrupted nighttime sleep and sleep instability in narcolepsy. J Clin Sleep Med. 2022;18:289–304. https://doi.org/10.5664/jcsm.9638

  51. • McAlpine CS, Kiss MG, Rattik S, et al. Sleep modulates haematopoiesis and protects against atherosclerosis. Nature. 2019;566:383–7. (This study on animal models provided the first evidence of a link between orexin deficiency and increased atherosclerosis burden.)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Dauvilliers Y, Beziat S, Pesenti C, et al. Measurement of narcolepsy symptoms the Narcolepsy Severity Scale. Neurology. 2017;88:1358–65.

  53. Plazzi G, Ferri R, Antelmi E, et al. Restless legs syndrome is frequent in narcolepsy with cataplexy patients. Sleep. 2010;33:689–94.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Dauvilliers Y, Pennestri M-H, Petit D, Dang-Vu T, Lavigne G, Montplaisir J. Periodic leg movements during sleep and wakefulness in narcolepsy. J Sleep Res. 2007;16:333–9.

    Article  PubMed  Google Scholar 

  55. Plazzi G, Ferri R, Franceschini C, Vandi S, Detto S, Pizza F, Poli F, De Cock VC, Bayard S, Dauvilliers Y. Periodic leg movements during sleep in narcoleptic patients with or without restless legs syndrome. J Sleep Res. 2012;21:155–62.

    Article  PubMed  Google Scholar 

  56. Dauvilliers Y, Jennum P, Plazzi G. Rapid eye movement sleep behavior disorder and rapid eye movement sleep without atonia in narcolepsy. Sleep Med. 2013;14:775–81.

    Article  PubMed  Google Scholar 

  57. • Barateau L, Jaussent I, Lopez R, Evangelista E, Chenini S, Benkiran M, Mariano-Goulart D. Dauvilliers Y. Cardiac sympathetic activity differentiates idiopathic and symptomatic rapid eye movement sleep disorder. Sci Rep. 2018;8(1):7304. (This study found a difference in cardiac scintigraphy between patients with NT1 and RBD and patients with idiopathic RBD, supporting different processes involved in RBD pathogenesis.)

  58. • Barateau L, Lopez R, Chenini S, Evangelista E, Benkiran M, Mariano-Goulart D, Jaussent I, Dauvilliers Y. Exploration of cardiac sympathetic adrenergic nerve activity in narcolepsy. Clin Neurophysiol. 2019;130:412–8. (This study found evidence of normal cardiac sympathetic innervation in NT1.)

    Article  PubMed  Google Scholar 

  59. Clark RW, Boudoulas H, Schaal SF, Schmidt HS. Adrenergic hyperactivity and cardiac abnormality in primary disorders of sleep. Neurology. 1980;30:113–9.

  60. Yoss RE, Moyer NJ, Ogle KN. The pupillogram and narcolepsy. A method to measure decreased levels of wakefulness. Neurology. 1969;19:921–8.

  61. Karacan I. Erectile dysfunction in narcoleptic patients. Sleep. 1986;9:227–31.

    Article  CAS  PubMed  Google Scholar 

  62. Wang J, Yan Z, Dong X, Li J, Zhao L, Zhang X, Lv C, Zhao Z, Strohl KP, Han F. Diurnal changes in blood pressure and heart rate in children with narcolepsy with cataplexy. J Sleep Res. 2023;32:e13736.

  63. • Jagadish S, Singer W, Kotagal S. Autonomic dysfunction in childhood hypersomnia disorders. Sleep Med. 2021;78:43–8. (This study reported a high prevalence of orthostatic hypotension in pediatric patients with hypersomnia disorders.)

    Article  PubMed  Google Scholar 

  64. Baumann-Vogel H, Schreckenbauer L, Valko PO, Werth E, Baumann CR. Narcolepsy type 2: A rare, yet existing entity. J Sleep Res. 2021;30:e13203.

  65. Barateau L, Lopez R, Chenini S, Rassu A-L, Scholz S, Lotierzo M, Cristol J-P, Jaussent I, Dauvilliers Y. Association of CSF orexin-A levels and nocturnal sleep stability in patients with hypersomnolence. Neurology. 2020;95:e2900–e2911. https://doi.org/10.1212/WNL.0000000000010743

  66. Lopez R, Barateau L, Rassu AL, Evangelista E, Chenini S, Scholz S, Jaussent I, Dauvilliers Y. Rapid eye movement sleep duration during the multiple sleep latency test to diagnose hypocretin-deficient narcolepsy. Sleep. 2023;46:zsac247.

  67. Aslan S, Erbil N, Tezer FI. Heart rate variability during nocturnal sleep and daytime naps in patients with narcolepsy type 1 and type 2. J Clin Neurophysiol. 2019;36:104–111. https://doi.org/10.1097/WNP.0000000000000544

  68. Dauvilliers Y, Bogan RK, Arnulf I, Scammell TE, St Louis EK, Thorpy MJ. Clinical considerations for the diagnosis of idiopathic hypersomnia. Sleep Med Rev. 2022;66:101709.

    Article  CAS  PubMed  Google Scholar 

  69. Evangelista E, Lopez R, Barateau L, Chenini S, Bosco A, Jaussent I, Dauvilliers Y. Alternative diagnostic criteria for idiopathic hypersomnia: a 32-hour protocol. Ann Neurol. 2018;83:235–47.

    Article  CAS  PubMed  Google Scholar 

  70. Lopez R, Doukkali A, Barateau L, Evangelista E, Chenini S, Jaussent I, Dauvilliers Y. Test–retest reliability of the multiple sleep latency test in central disorders of hypersomnolence. Sleep. 2017;40:zsx164.

    Article  Google Scholar 

  71. Adra N, Reddy M, Attarian H, Sahni AS. Autonomic dysfunction in idiopathic hypersomnia: an overlooked association and potential management. J Clin Sleep Med. 2022;18:963–5.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Bassetti C, Aldrich MS. Idiopathic hypersomnia. A series of 42 patients. Brain. 1997;120(Pt 8):1423–35.

    Article  PubMed  Google Scholar 

  73. Vernet C, Leu-Semenescu S, Buzare M-A, Arnulf I. Subjective symptoms in idiopathic hypersomnia: beyond excessive sleepiness. J Sleep Res. 2010;19:525–34.

    Article  PubMed  Google Scholar 

  74. Baker TL, Guilleminault C, Nino-Murcia G, Dement WC. Comparative polysomnographic study of narcolepsy and idiopathic central nervous system hypersomnia. Sleep. 1986;9:232–42.

    Article  CAS  PubMed  Google Scholar 

  75. Sforza E, Roche F, Barthélémy JC, Pichot V. Diurnal and nocturnal cardiovascular variability and heart rate arousal response in idiopathic hypersomnia. Sleep Med. 2016;24:131–6.

    Article  PubMed  Google Scholar 

  76. • Miglis MG, Schneider L, Kim P, Cheung J, Trotti LM. Frequency and severity of autonomic symptoms in idiopathic hypersomnia. J Clin Sleep Med. 2020;16:749–56. (This study reported that symptoms of autonomic nervous system dysfunction, as assessed with the COMPASS-31 score, are common in patients with idiopathic hypersomnia.)

    Article  PubMed  PubMed Central  Google Scholar 

  77. Parsaik A, Allison TG, Singer W, Sletten DM, Joyner MJ, Benarroch EE, Low PA, Sandroni P. Deconditioning in patients with orthostatic intolerance. Neurology. 2012;79:1435–9.

  78. Arnulf I, Rico TJ, Mignot E. Diagnosis, disease course, and management of patients with Kleine-Levin syndrome. Lancet Neurol. 2012;11:918–28.

    Article  PubMed  Google Scholar 

  79. Dauvilliers Y, Mayer G, Lecendreux M, Neidhart E, Peraita-Adrados R, Sonka K, Billiard M, Tafti M. Kleine-Levin syndrome: an autoimmune hypothesis based on clinical and genetic analyses. Neurology. 2002;59:1739–45.

  80. Ambati A, Hillary R, Leu-Semenescu S, et al. Kleine-Levin syndrome is associated with birth difficulties and genetic variants in the TRANK1 gene loci. Proc Natl Acad Sci U S A. 2021;118:e2005753118.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Lopez R, Barateau L, Chenini S, Dauvilliers Y. Preliminary results on CSF biomarkers for hypothalamic dysfunction in Kleine-Levin syndrome. Sleep Med. 2015;16:194–6.

    Article  PubMed  Google Scholar 

  82. • Wang JY, Han F, Dong SX, et al. Cerebrospinal Fluid Orexin A Levels and Autonomic Function in Kleine-Levin Syndrome. Sleep. 2016;39:855–60. (This study found lower orexin A levels in the cerebrospinal fluid in the symptomatic phase of the Kleine-Levin syndrome than in remission.)

    Article  PubMed  PubMed Central  Google Scholar 

  83. Barateau L, Dauvilliers Y. Recent advances in treatment for narcolepsy. Ther Adv Neurol Disord. 2019;12:1756286419875622.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Barateau L, Dauvilliers Y. Hypersomnias of central origin. Treatment: Sleep Medicine Textbook, European Sleep Research Society; 2021.

    Google Scholar 

  85. Thorpy MJ, Shapiro C, Mayer G, et al. A randomized study of solriamfetol for excessive sleepiness in narcolepsy. Ann Neurol. 2019;85:359–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Dauvilliers Y, Arnulf I, Szakacs Z, Leu-Semenescu S, Lecomte I, Scart-Gres C, Lecomte J-M, Schwartz J-C, HARMONY III study group. Long-term use of pitolisant to treat patients with narcolepsy: Harmony III Study. Sleep. 2019;42:zsz174. https://doi.org/10.1093/sleep/zsz174

  87. Bogan RK, Thorpy MJ, Dauvilliers Y, Partinen M, Del Rio Villegas R, Foldvary-Schaefer N, Skowronski R, Tang L, Skobieranda F, Šonka K. Efficacy and safety of calcium, magnesium, potassium, and sodium oxybates (lower-sodium oxybate [LXB]; JZP-258) in a placebo-controlled, double-blind, randomized withdrawal study in adults with narcolepsy with cataplexy. Sleep. 2021;44:zsaa206. https://doi.org/10.1093/sleep/zsaa206

  88. Dauvilliers Y, Arnulf I, Foldvary-Schaefer N, et al. Safety and efficacy of lower-sodium oxybate in adults with idiopathic hypersomnia: a phase 3, placebo-controlled, double-blind, randomised withdrawal study. Lancet Neurol. 2022;21:53–65.

    Article  CAS  PubMed  Google Scholar 

  89. Evans R, Kimura H, Alexander R, et al. Orexin 2 receptor-selective agonist danavorexton improves narcolepsy phenotype in a mouse model and in human patients. Proc Natl Acad Sci U S A. 2022;119:e2207531119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Biomedical and Neuromotor Sciences, University of Bologna, Ravenna Campus, Ravenna, Italy

    Alessandro Silvani

  2. Epileptology and Cerebral Rhythmology, Sleep Unit, APHM, Timone Hospital, Marseille, France

    Isabelle Lambert

  3. Inserm, INS, Aix-Marseille Univ, Inst Neurosci Syst, Marseille, France

    Isabelle Lambert

  4. Johannes-Kepler University Linz, Department of Neurology, Linz, Austria

    Anna Heidbreder

  5. National Reference Center for Narcolepsy and Rare Hypersomnias, Gui-de-Chauliac University Hospital, Montpellier, France

    Yves Dauvilliers & Lucie Barateau

  6. Institute for Neurosciences of Montpellier (INM), Université de Montpellier, Montpellier, Inserm, France

    Yves Dauvilliers & Lucie Barateau

  7. Sleep Disorders Center, Department of Neurology, Gui-de Chauliac Hospital, CHU Montpellier, 80 Avenue Augustin Fliche, Cedex 5, 34295, Montpellier, France

    Lucie Barateau

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Correspondence to Lucie Barateau.

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Conflict of Interest

Alessandro Silvani is an inventor in Italian patent application n. 102022000013894 related to a novel dual orexin receptor agonist and received speaker fees related to Idorsia and Bioprojet. Isabelle Lambert declares that she has no conflict of interest related to this article. Anna Heidbreder declares that she has no conflict of interest related to this article. Yves Dauvilliers declares that he has no conflict of interest related to this article; he received funds for seminars, board engagements, and travel to conferences by UCB Pharma, Jazz, Theranexus, Idorsia, Takeda, Avadel, and Bioprojet. Lucie Barateau declares that she has no conflict of interest related to this article; she received funds for traveling to conferences by UCB Pharma, Idorsia, and Bioprojet, and board engagements by Jazz, Takeda, Idorsia, and Bioprojet.

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Silvani, A., Lambert, I., Heidbreder, A. et al. Autonomic Dysfunction in Hypersomnia. Curr Sleep Medicine Rep 9, 115–123 (2023). https://doi.org/10.1007/s40675-023-00251-y

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  • DOI: https://doi.org/10.1007/s40675-023-00251-y

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